Modulation of the oncogenic potential of β-catenin by the subcellular distribution of plakoglobin

✍ Scribed by Laiji Li; Kimberly Chapman; Xiuying Hu; Annissa Wong; Manijeh Pasdar

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 573 KB
• Volume: 46
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/mc.20310

✦ Synopsis

Abstract

Plakoglobin (Pg) and β‐catenin are homologous proteins that function in cell–cell adhesion and signaling. The cadherin‐associated form of these proteins mediates adhesion, whereas the cytosolic/nuclear form has a signaling role. Despite their interactions with common cellular partners, β‐catenin has a well‐documented oncogenic potential while Pg has a less characterized tumor suppressor activity. We showed previously that Pg overexpression in Pg‐deficient SCC9 cells (SCC9‐Pg‐WT) induced Bcl‐2 expression and inhibited apoptosis. To assess the exact role of Pg in Bcl‐2 expression, we generated and characterized SCC9 transfectants expressing Pg with a restricted cytoplasmic (Pg‐NES) or nuclear (Pg‐NLS) distribution. We show that Bcl‐2 was expressed regardless of Pg localization, although its level was substantially lower in SCC9‐Pg‐NLS cells. Bcl‐2 expression coincided with increased nuclear β‐catenin levels (Pg‐NES) or a decrease in the level of total and nuclear β‐catenin associated with N‐cadherin and α‐catenin (Pg‐WT and ‐NLS) cells. Bcl‐2 expression also was induced in SCC9 cells overexpressing β‐catenin. In contrast, SCC9 cells expressing mutant Pg proteins, unable to interact with N‐cadherin and α‐catenin, had noticeably lower Bcl‐2 levels. Our data suggest that Bcl‐2 expression is induced by β‐catenin and modulated by Pg. We show that the inhibition of β‐catenin‐dependent TCF transactivation had no effect on Bcl‐2 levels, suggesting that induction of Bcl‐2 expression by β‐catenin and its modulation by Pg may involve factors other than, or in addition, to, TCF. These results provide a possible mechanism for the tumor suppressor activity of Pg via its role as a regulator of the oncogenic potential β‐catenin. © 2007 Wiley‐Liss, Inc.